Production of murine monoclonal antibodies to human cell surface proteins has resulted in the definition of several virus receptors on the surface of human cells. Some of these proteins are important in the function of T and B cells. CR2 has been identified as the EBV receptor, CD4 as the HIV receptor and ICAM-1 as the major rhinovirus receptor. Echoviruses (members of the human picornavirus family) are non-enveloped RNA viruses which cause aseptic meningitis in adults and fetal disseminated infections in neonates. For other picornaviruses, tissue tropism and the spectrum of clinical illness is determined by tissue expression of specific receptors for virus attachment. Receptors for echoviruses have not been defined. We have produced murine monoclonal antibodies, directed against human cell surface components, that block echovirus attachment. These antibodies immunoprecipitate human cell surface proteins of 125 and 145 Kd. We will use these antibodies and others to define the human echovirus receptor. Candidate receptor proteins will be biochemically characterized, cloned and expressed in mammalian cells to examine their ability to mediate virus attachment and internalization. These studies will allow for the development of animal models of disease and characterization of the function of the cell protein(s) involved in binding.